The proposed study will attempt to identify and characterize the mechanism of action of cholecystokinin (CCK) on gallbladder and intestinal smooth muscle. The action of CCK will be assessed by measuring its effect on smooth muscle contraction and calcium flux. The effects of CCK on smooth muscle will be compared to the effects of other cholecystokinetic agents. By attempting to discern the mechanism by which dibutyryl cyclic GMP specifically inhibits smooth muscle contraction caused by CCK peptides, we hope to gain information how CCK acts at its receptor. Besides studying the initial steps in the contractile process induced by CCK, we plan to study the persistently stimulated state of smooth muscle contraction caused by CCK. That is, the mechanism by which CCK causes persistent stimulation of smooth muscle contraction after the peptide has been removed from the incubation medium. Finally, we plan to compare the biologic activity and chemical properties of the factor(s) in human serum which causes gallbladder contraction and pancreatic amylase release with those of synthetic CCK octapeptide (CCK8) and purified porcine native CCK (CCK33). By performing these studies we hope to resolve the difference between serum CCK levels measured by radioimmunoassay and those by bioassay and determine whether CCK is the major cholecystokinetic agent in human serum (which has recently been disputed). Studies are planned to examine further our preliminary observations that serum CCK may be bound to a serum protein and to determine if the bound state alters the peptide's biologic activity.